In our co-pending patent application No. SG 200903301-0 filed on 14 May 2009 the priority of which is hereby claimed, we disclosed a novel composition comprising lycopene and resveratrol in certain ratios or proportions that have shown synergistic effect in inhibiting cancerous growths in mammals. The specific anti-neoplastic mechanism aided by our compositions was then unknown.
A mammalian body's innate immune response is provided by NK cells which are large granular lymphocytes (LGLs) providing immuno-surveillance of any cells of the body turning cancerous or that has been infected by a pathogen, or a foreign body, e.g. transplanted tissue. As first line innate defence, NK cells do not require antigen-dependent activation. Its immunosurveillance function works by seeking out cells distressed by pathogen infection or had turned cancerous, and killing these cells by cytotoxic or cytolytic means, i.e. by releasing cytoplasmic protein granules such as perforin and granzyme that are cytotoxic to the target cells causing them to die by apoptosis such as cytolysis.
Given their strong cytolytic activity and potential auto-activity, NK cell activity is tightly regulated wherein it must receive a triggering biochemical signal in order to be activated. The biochemical trigger includes double-stranded RNA, cytokines, Fc receptor and other applicable ligand receptors. Tumour risk is thus taken to be inversely related to NK cell population level or activity.
Prior art known to us that attempted to activates NK cell activity via biochemical signalling are as follows. U.S. Pat. No. 4,883,662 (Stout) discloses the use of a biologic to boost the population of NK cells in patients suffering from cancer. The biologics are produced by introducing a strain of immunosuppressive virus into an animal, thereby stimulating the animal to produce the desired biologics which may be harvested and fractionated or purified for administration into the blood stream of cancer patients by injection.
U.S. Pat. No. 5,728,378 (Hellstrand) details a combination of cytokine, interferon-α and a composition containing histamine and serotonin as a pharmaceutical preparation to increase the activity of NK cells in the presence of monocytes. The preparation is administered by local or systemic injection or infusion into the bloodstream of the patients suffering from cancer or viral-infections. The preparation acts synergistically in elevating the activity of NK cells wherein the composition containing histamine and serotonin functions in suppressing monocytes activities therefore enabling the activation of NK cells by interferon-α.
In a subsequent U.S. Pat. No. 6,063,373 (Hellstrand), a combination consisting NK cells activators and an intracellular hydrogen peroxide inhibitor is employed for enhancing NK cells activities in the presence of monocytes. The NK cell activators are selected from the group of cytokines comprising Interleukin-1 (IL-1), Interleukin-2 (IL-2), Interleukin-12 (IL-12), Interleukin-15 (IL-15), Interferon-α (IFN-α), Interferon-β (IFN-β), or Interferon-γ (IFN-γ). The activators may also be in the form of flavonoids selected from the group consisting flavone-8 acetic acid (FAA) and xanthenone-4 acetic acid (XAA). Meanwhile the intracellular hydrogen inhibitors are selected from histamine, hydrogen receptor agonist and serotonin.
Not many disclosures relating to plant-based dietary compositions that might be enhancing NK cell activity—either by way of NK cell proliferation or elevating their activity—for purposes of effective therapeutic treatment for tumours and infections have been found. In European Patent EP-1,243,274 (Lu Kung-Ming) it is suggested that aqueous soy extract fermented by a particular bacteria strain of the genus Lactobacillus or optionally by a Saccharomyces cerevisiae yeast would induce cell apoptosis. In United States Patent Publication US 2002/010149 (Yagita), it is described that the mycelia of Lentinus edodes (also known as shiitake) may induce IL-12 production which activates NK cells. In PCT patent publication No. WO 2007/131767 (Goral-Czyk) a combination of lycopene and genistein for therapy of prostate carcinoma wherein one of the embodiments may optionally include resveratrol without suggesting affect on NK cell activity.